Virus-induced respiratory disease accounts for the majority of hospitalizations of young children during the winter months. The major viral causes of lower respiratory tract disease in infants and children are respiratory syncytial virus (RSV), rhinovirus, metapneumovirus (hMPV), parainfluenza virus 3 (PIV-3), and influenza. The primary antiviral mechanism involves the activation of cytotoxic T cells and the clearance of virus-infected epithelial cells, and Toll-like receptors that recognize microbial molecular patterns are thought to initiate and orchestrate the immune response. Here, we review the role of Toll-like receptors in modulating the immune response to respiratory viral disease, including the role of maturation of the TLR system in early life.